TY - JOUR
T1 - Mechanisms of high-density lipoprotein reduction after probucol treatment
T2 - Changes in plasma cholesterol esterification/transfer and lipase-activities
AU - Chiesa, Giulia
AU - Michelagnoli, Silvia
AU - Cassinotti, Michela
AU - Gianfranceschi, Gemma
AU - Werba, JoséP
AU - Pazzucconi, Franco
AU - Sirotori, Cesare R.
AU - Franceschini, Guido
PY - 1993
Y1 - 1993
N2 - Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo) A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.
AB - Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo) A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.
UR - http://www.scopus.com/inward/record.url?scp=0027412709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027412709&partnerID=8YFLogxK
U2 - 10.1016/0026-0495(93)90041-L
DO - 10.1016/0026-0495(93)90041-L
M3 - Article
C2 - 8474321
AN - SCOPUS:0027412709
VL - 42
SP - 229
EP - 235
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 2
ER -